title: Ionic complexation as a non-covalent approach for the design of folate anchored rifampicin Gantrez nanoparticles.
abstract: The present study discloses the design of folate anchored Rifampicin-Poly methylvinylether maleic anhydride copolymer (Gantrez AN-119, Gantrez) nanoparticles (RFMGzFa) by ionic complexation. Folic acid was anchored to the preformed drug loaded nanoparticles. Folic acid was anchored in different concentration by simply varying the amount of folic acid added during preparation. RFMGzFa nanoparticles were prepared by emulsion solvent diffusion method. Gantrez AN-119 rapidly hydrolyzes in aqueous medium releasing carboxylic acid groups, to create an acidic environment. This facilitates protonation and subsequent ionic complexation of folic acid with the carboxylic groups, to enable anchoring. FTIR spectra confirmed this interaction. Infrared imaging revealed distribution of folic acid across the nanoparticle surface. Nanoparticles were obtained in the size range 350-450 nm with RFM loading of 12-14% w/w. Zeta potential confirmed colloidal stability. TEM/SEM revealed spherical morphology. RFMGzFa nanoparticles exhibited sustained release of RFM and folic acid. Folic acid showed sustained release upto 12 h, which was ion exchange mediated. A 480% enhancement in RFM uptake with RFMGzFa nanoparticles compared to 300% with RFMGz nanoparticles in-vitro, in human macrophage cell line U-937, suggested the role of folic acid in folate receptor mediated uptake. Ionic complexation represents a simple non-covalent approach for anchoring folic acid on polymeric nanoparticles of Gantrez.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, Maharashtra, India.
authors.forename: Praveen V
authors.initials: PV
authors.lastname: Date
authors.forename: Mitesh D
authors.initials: MD
authors.lastname: Patel
authors.forename: Sharmila B
authors.initials: SB
authors.lastname: Majee
authors.forename: Abdul
authors.initials: A
authors.lastname: Samad
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D015195:Drug Design; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D046911:Macromolecular Substances / Q000138:chemical synthesis* / Q000737:chemistry; D008298:Maleates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D011145:Polyvinyls / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D020298:U937 Cells
chemical_list: D000904:Antibiotics, Antitubercular; D003879:Dermatologic Agents; D007477:Ions; D046911:Macromolecular Substances; D008298:Maleates; D011145:Polyvinyls; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; D005492:Folic Acid; D012293:Rifampin